tbuckley/cabot-search huggingface dataset:
Trial in progress: Phase II activity trial of high-dose radiation and chemosensitization in patients with macrometastatic lymph node spread after sentinel node biopsy in vulvar cancer: Groningen International Study on Sentinel Nodes in Vulvar Cancer III (GROINSS-V III/NRG-GY024).
Authors: Lilian Tran Gien, Brian M. Slomovitz, Mario M. Leitao, Ate Van Der Zee, Carien L. Creutzberg, An K.L Reyners, Petronella Witteveen, Diandra Ayala-Peacock, Jyoti Mayadev, Charles A. Leath, Maaike Oonk
Journal: Journal of Clinical Oncology (2022)

TPS5624 Background: Early stage invasive squamous cell carcinoma of the vulva is treated by radical excision of the primary tumor combined with a sentinel node (SN) procedure for the groins. GROINSS-VI and GOG-173 demonstrated that if there is no metastasis to the SN, then standard of care is observation. GROINSS-VII/GOG-270 demonstrated that micrometastatic disease (&lt;2mm) to the SN requires standard radiotherapy (50 Gy) without the need for an inguinofemoral lymphadenectomy (IFL). This study also found that patients with macrometastasis ( &gt; 2mm) required IFL in order to have an acceptably low groin recurrence rate. However, IFL is associated with significant morbidity such as lymphedema, wound healing issues, and recurrent infections. It is hypothesized that for those with macrometastasis ( &gt; 2 mm) in the SN, the efficacy of treatment can be increased by giving a higher dose of radiotherapy along with chemosensitization. Methods: This is an international multicenter single-arm phase II prospective clinical trial. The primary objective is to investigate the safety of replacing IFL by chemoradiation in early-stage vulvar cancer patients with a macrometastasis ( &gt; 2mm) and/or extracapsular extension in the SN. The primary endpoint is the groin recurrence rate in the first two years after primary treatment. Secondary endpoints are short and long-term morbidity associated with the SN procedure and chemoradiation and quality of life as measured by EORTC-QLQc30. Patients with invasive ( &gt; 1mm) squamous cell carcinoma of the vulva, stage T1, tumor size &lt; 4 cm diameter and no suspicious lymph nodes by imaging of the groins will proceed with SN detection. Institutions enrolling patients must demonstrate prior surgical experience with SN detection with the submission of at least 10 successfully completed cases in vulvar cancer. Patients with SN metastases &gt; 2mm and/or with extracapsular extension or those with &gt; 1 SN with micrometastases will be eligible for this study. Treatment will consist of chemoradiation with a dose of 56 Gy to the groin combined with weekly cisplatin 40 mg/m2 IV on days 1, 8, 15, 21 and 29 of radiotherapy. One hundred and fifty-seven patients in Europe, United States and Canada will be enrolled. The study includes continuous monitoring of groin recurrences with stopping rules. Results of this trial may be practice changing and eliminate the need for IFL in all women with clinically early stage vulvar cancer. The study is currently open for enrollment. Clinical trial information: NCT05076942.
The impact of different WHO reference criteria for semen analysis in clinical practice: Who will benefit from the new 2021 cutoffs for normal sperm parameters?
Authors: L. Boeri, E. Pozzi, F. Belladelli, G. Fallara, M. Raffo, C. Corsini, L. Candela, A. Costa, D. Cignoli, N. Schifano, A. D'Arma, E. Ventimiglia, P. Capogrosso, F. Dehó, V. Mirone, L. Pagliardini, E. Papaleo, F. Montorsi, A. Salonia
Journal: European Urology (2022)
Effect of Point-of-Care Testing for Respiratory Pathogens on Antibiotic Use in Children
Authors: Suvi Mattila, Niko Paalanne, Minna Honkila, Tytti Pokka, Terhi Tapiainen
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Limited data are available on the clinical impact of multiplex polymerase chain reaction (PCR) point-of-care testing for respiratory pathogens in acutely ill children. <h3>Objective</h3> To evaluate the effect of multiplex PCR point-of-care testing for respiratory pathogens on antibiotic use in acutely ill children. <h3>Design, Setting, and Participants</h3> This unblinded, randomized clinical trial was conducted from May 6, 2019, through March 12, 2020. The participants were followed up until hospitalization or discharge from the emergency department (ED) for primary outcome. The study was conducted at the pediatric ED of Oulu University Hospital, Finland. Eligible study participants were children aged 0 to 17 years with fever and/or any respiratory signs or symptoms. Children with underlying medical conditions were included. The statistical analyses were performed between August 11, 2020, and September 14, 2021. <h3>Interventions</h3> The participants were randomly assigned in a 2:1 ratio either to undergo multiplex PCR point-of-care testing (18 respiratory viruses and 3 bacteria with results ready within 70 minutes) upon arrival at the ED or to receive routine care. <h3>Main Outcomes and Measures</h3> The primary outcome was the proportion of children receiving antibiotic therapy. The secondary outcomes were the numbers of diagnostic tests and radiographic imaging procedures performed and costs. <h3>Results</h3> A total of 1417 children were assessed for eligibility. After exclusions, 1243 children (692 boys [56%]) were randomly allocated to either the intervention (829 children) or control (414 children) group. The mean (SD) age of the participants was 3.0 (3.6) years in the intervention group (median [IQR], 1.7 [0.4-4.1] years) and 3.0 (3.5) years (median [IQR], 1.9 [0.4-4.1] years) in the control group. Multiplex PCR point-of-care testing for respiratory pathogens did not reduce the overall prescribing of antibiotics in the emergency department (226 children [27.3%] in the intervention group vs 118 children [28.5%] in the control group; risk ratio, 0.96; 95% CI, 0.79-1.16). Targeted antibiotic therapy was started in 12 children (1.4%) tested with point-of-care multiplex PCR and 2 children (0.5%) in the control group (risk ratio, 3.0; 95% CI, 0.76-11.9). The numbers of diagnostic tests did not differ between the groups, nor did the costs. <h3>Conclusions and Relevance</h3> In this randomized clinical trial, point-of-care testing for respiratory pathogens did not reduce the use of antibiotics at the pediatric ED. Testing for respiratory pathogens appears to have a limited impact on clinical decision-making for acutely ill children. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT03932942
Randomized controlled trial (RCT) of symptom screening with targeted early palliative care (STEP) versus usual care in patients with advanced cancer.
Authors: Camilla Zimmermann, Ashley Pope, Breffni Hannon, Monika K. Krzyzanowska, Gary Rodin, Madeline Li, Doris Howell, Jennifer J. Knox, Natasha B. Leighl, Srikala S. Sridhar, Amit M. Oza, Rebecca M. Prince, Stephanie Lheureux, Aaron Richard Hansen, Neesha C. Dhani, Geoffrey Liu, Philippe L. Bedard, Eric Xueyu Chen, Nadia Swami, Lisa W Le
Journal: Journal of Clinical Oncology (2022)

e24084 Background: To direct limited specialized palliative care resources to patients in greatest need, we developed STEP (Symptom screening with Targeted Early Palliative care). STEP entails symptom screening (ESAS-r) at each oncology clinic visit and triggered alerts (for moderate-high physical and psychological symptoms) to a nurse who calls the patient to offer a palliative care clinic (PCC) visit. We conducted a phase III RCT to assess the impact of STEP versus usual care on quality of life and other patient-reported outcomes (PROs). Methods: Adults with advanced cancer were recruited from medical oncology clinics at the Princess Margaret Cancer Centre, Toronto, Canada. Consenting patients with oncologist-assessed ECOG 0-2 and estimated survival of 6-36 months were enrolled and block randomized (stratified by tumour site and symptom severity) to STEP or usual care. Participants completed measures of quality of life (FACT-G7), depression (PHQ-9), symptom control (ESASr-CS), and satisfaction with care (FAMCARE-P16) at baseline, 2, 4 and 6 months. The primary outcome was FACT-G7 at 6 months, with a planned sample size of 261/arm. Results: From 8/2019 to 3/2020, 69 patients were enrolled: 33 randomized to STEP and 36 to usual care. The trial was then halted permanently due to the COVID-19 pandemic, owing to substantial changes to elements of STEP (shift to virtual symptom screening and palliative care) and usual care (shift to virtual oncology care). Median age was 64 years (range 25-87) and 62% (43/69) were women; study arms were balanced at baseline except gender, with more women randomized to STEP. Within the STEP arm, 20 (61%) participants triggered a nurse’s call to offer a PCC visit, of whom 13 attended the clinic at least once. All outcomes tended to be better in the STEP arm compared to usual care, particularly depression and satisfaction with care at 6 months; however, results were not statistically significant (Table). Conclusions: STEP holds promise for improving quality of life and other PROs in patients with advanced cancer and effectively directing early palliative care towards those who need it most. In response to the pandemic, an online version of STEP has been developed and a further trial is in progress. Clinical trial information: NCT03987906. [Table: see text]
QOL-01. Inflammatory biomarkers and psychological sequela in pediatric brain tumor survivors
Authors: Emily Turner, Sonal Johal, Gailen Marshall, Betty Herrington, Jannie Criddle, Alyssa Reddy, Anju Sukumaran, Youssef Al Hmada, James M Shiflett, Cynthia Karlson
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND AND AIMS: Pediatric brain tumors are the second most common type of pediatric cancer, and these patients face the worst health related quality of life (HRQOL) outcomes. Adult studies show increased inflammation association with lower HRQOL in adult brain tumor survivors. This relationship has not been explored in pediatric brain tumor survivors (PBTS). We conducted a case-control study to explore the relationship between inflammatory biomarkers and psychological sequela (i.e., sleep disturbance, fatigue, pain, negative affect) in PBTS. METHODS: Survivors aged 7-14 years with a primary brain tumor diagnosis were recruited from UMMC (N=29) and UAB (N=4) between 2016-2019. A control group (N=12) was recruited from UMMC well-child appointments. Parents and children completed self-reported surveys of pain, sleep, fatigue, and mood. The primary aims were to: (1) examine levels of C-reactive protein (CRP) inflammation in PBTS compared to controls (2) examine if higher CRP and SOX2 (from tumor tissue) were associated with psychological sequela. Independent samples T-Tests and spearman correlations evaluated aims. RESULTS: The final sample included 33 PBTS: median age=12.42 years; sex=51.5% female; race=63.6% Caucasian, 33.3% African American; pathologic diagnoses=67% astrocytoma/glioma, 11% medulloblastoma, 6% ependymoma, 12% other. Twelve controls had a median age=11.98 years; sex=41.7% female; race=16.7% Caucasian, 83.8% African American. There were marginal elevations in CRP for PBTS (44%, n=13) compared to controls (13%, n=1) (p=0.06). In PBTS, higher CRP levels were associated with greater parent-reported fatigue (p=0.035), sleep-wake disorders (p=0.017), excessive somnolence (p=0.042) and longer pain duration (p=0.037). From 13 tumor samples, positive SOX2 (69% of samples) was associated with increased parent-reported sleep-wake disorders (p=0.016), excessive somnolence (p=0.036), and both child and parent-reported sleep disturbance (child: p=0.014; parent: p=0.034). CONCLUSIONS: Elevated inflammation in PBTS, up to 9 years post-treatment, is consistently associated with increased sleep disturbance and fatigue. These relationships warrant further investigation in PBTS.
Renal cell carcinoma in renal transplant recipients: Is there a role for screening?
Authors: Binoy Yohannan, Arthi Sridhar, Harmanpreet Kaur, Aleksandra De Golovine, Neha Maithel
Journal: Journal of Clinical Oncology (2022)

10528 Background: Renal transplant (RT) recipients are at an increased risk of developing renal cell carcinoma (RCC), mainly due to iatrogenic immunosuppression and changes in immune surveillance. Most RCCs in RT recipients arises from the native kidney, but rarely may arise from the allograft. RCC post-RT can adversely affect allograft function and long-term survival. Screening for RCC in RT recipients is controversial and is not routinely done. Methods: We performed a retrospective chart review of RT recipients who underwent transplantation between January 1, 1999, and December 31, 2019. The following data were collected: Baseline demographic variables, cause of end-stage renal disease (ESRD), duration of dialysis prior to RT, type of RT (cadaveric vs. living donor), immunosuppressive regimen, site of RCC (native kidney vs transplanted kidney), time from RT to diagnosis of RCC, stage and Fuhrman grade, tumor histology, RCC treatment, and RCC-related mortality. RCC stage at diagnosis and survival were compared between patients who were screened versus those who were not. Results: Among 1998 RT recipients who underwent transplantation at Memorial Hermann Hospital (MHH) Texas Medical Center (TMC); 16 patients (0.8%) developed RCC. An additional 4 patients with RCC who underwent RT elsewhere but received follow up at MHH TMC were also included. Therefore, a total of 20 patients with post-RT RCC were identified, of whom 75% were men. Subject races included White (20%), Black (50%), Hispanic (20%), and Asian (10%). The median age was 56 years. Median duration of dialysis prior to RT was 36 months (range, 1–120). Median time to RCC diagnosis post-RT was 96 months (range, 16–312). Histologies included clear cell (75%), papillary (20%), and chromophobe (5%) RCC. RCC developed in the native kidney in 60% and in the allograft in 40% of the patients. Post-RT RCC patients were divided into those who underwent regular screening (n = 12) and no screening (n = 8). The regular screening group (n = 12) underwent ultrasound or computerized tomography annually or every 2 years. All of these patients had early-stage disease at presentation: stage I (n = 11) or II (n = 1). All patients who had RCC detected by screening were cured by nephrectomy (n = 10) or cryotherapy (n = 2). In patients who had no screening post RT, 37.5% had stage I, 25% had stage III, and 37.5% had stage IV RCC. Two patients with stage IV RCC died from metastatic disease. The RCC-related mortality was 0% in patients who were screened, compared to 25% in patients who had no screening. Conclusions: All RT recipients who had RCC diagnosed based on screening had an early diagnosis and no RCC-related mortality. Screening for RCC in RT recipients is an effective tool for early diagnosis and to reduce RCC-related mortality. Further research into the cost-effectiveness of screening is imperative.
Optic pathway gliomas in children: Demographic, clinical characteristics, and results of an adapted protocol.
Authors: Rejin Kebudi, Ulku Miray Yıldırım, Ayca Iribas, Samuray Tuncer
Journal: Journal of Clinical Oncology (2022)

e22016 Background: Optic pathway gliomas (OPG) constitute 1-5% of childhood brain tumors. The presence of neurofibromatosis type 1 (NF-1) is generally associated with more indolent disease. The aim of this study is to evaluate patients with optic pathway gliomas diagnosed/treated/ followed in a single center over 32 years. Methods: The medical files of 85 patients with OPG diagnosed/treated between 1990-2021 in the Istanbul University, Oncology Institute were retrospectively assessed for demographic, clinical characteristics, treatment and outcome. Results: The median age of the 85 patients (42 male, 43 female) was 60 (1-216) months, 53 (62.4%) had NF-1. Seven had diencephalic syndrome (8.2%). According to Dodge classification, 23 (27.1%) had Dodge 1, 30 (35.3%) Dodge 2 and 32 (37.6%) Dodge 3 disease. Median follow up time was 10.5 years (1-31 years). Twenty (23.5%) patients had stable disease and were followed without treatment, 14 patients underwent surgery (5 gross total tumor resection, 2 subtotal resection, 3 ventriculoperitoneal shunt operation, 4 excision/biopsy). 7 patients recieved radiotherapy (RT), none had NF1. 56 patients received chemotherapy (CT) due to severe/progressive clinical symptoms (such as diencephalic syndrome, visual impairment, nystagmus) or radiologic progressive disease. Chemotherapy consisted of an adapted SIOP-LGG regimen: vincristine (VCR) 1.5 mg/m²/dose and carboplatinum 550 mg/m²/dose every 21 days for three courses with weekly VCR, followed by VCR and carboplatinum every 28 days for a total of 12 cycles (3 cycles induction, 9 cycles consolidation). Vinblastin or cisplatinum with etoposide were used for second line or further treatment in progressive disease. One of the seven patients who had diencephalic syndrome and two of the 3 patients with leptomeningeal metastasis died. Ocular findings were recorded in 47 patients: vision was stable in 30 (63.8%), improved in 15 (31.9%), detoriated in 2 (4.3%). Radiology (MRI) revealed stable disease/regression of tumor in 41 patients, and complete regression of spinal metastasis in 1 patient. Endocrinologic follow-up was done and 13(15.2%) recieved hormonal treatment. Ten year overall survival(S) in all patients, in patients with NF1 and without NF1 were 96.5%, 96.1% and 95%, respectively; 10 year event free survival (EFS) in all patients, in patients with NF1 and without NF1 were 80.6%, 90.5% and 60% (p:0.001) respectively. Conclusions: OPG may remain indolent for many years after diagnosis, especially in patients with NF 1. However, these tumors develop progressive characteristics and can cause visual disturbances, endocrine dysfunction, blindness and even death among some of the patients. In young children who are symptomatic/have progressive disease, chemotherapy with an adapted regimen consisting of vincristine and carboplatinum seems to be effective and provides a relatively good quality of life.
MiR-6821-5p and coronary calcification in familial hypercholesterolemia patients with subclinical atherosclerosis
Authors: T Padro, R Escate, R Suades, P Mata, L Badimon
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Agencia Estatal de Investigaciópn (AEI)” - Spanish Ministry of Economy Competitiveness of Science Agencia Estatal de Investigaciópn (AEI)” - Spanish Institute of Health Carlos III, ISCIII Background Familial hypercholesterolemia (FH) is associated with premature atherosclerosis but FH patients have a highly variable risk of clinical atherosclerotic cardiovascular disease (ACVD) presentation. Preclinical atherosclerosis has been identified by imaging of coronary artery calcium (CAC); however, little is known of the molecular pathways involved in vascular calcification in FH. Circulating microRNAs are proven as a powerful epigenetic regulators of atherosclerosis development. Purpose We have investigated the circulating microRNA signature of FH patients with CAC and asymptomatic atherosclerosis. Methods Differential plasma miRNA profiling was performed by Affymetrix microarray technology (discovery studies) and RT-PCR using TaqMan technology (validation studies) in plasma of FH subjects (N=86) included in a multicentric nationwide cohort. FH-patients with and without coronary calcification (determined by Agatston score) by computed tomographic angiography imaging were investigated. Proof-of-concept validation studies were performed in cell culture of human coronary-derived vascular smooth muscle cells (hcVSMC) calcification analysis. Results Using a non-targeted approach, a differential signature of 15 miRNA (all upregulated) was identified in FH-patients presenting subclinical atherosclerosis with calcified plaques (FH-CCS+, N=49, Agatston score &amp;gt;100) compared with FH-subjects without coronary calcification (FH-CCS-, N=37, Agatston score 0). After RT-PCR validation, 3 miRNAs (miR-193a-5p, miR-30e-5p and miR-6821-5p) were significantly upregulated in FH-CCS+ patients. ROC-analysis confirmed miR-6821-5p as the best miRNA for discriminating FH-patients with coronary calcification (AUC 0.70±0.06, P=0.003). High miR-6821-5p levels associated to older age (P=0.003) and high LDL burden (P=0.014), two established risk factors for calcification. In vitro studies showed miR-6821-5p up-regulation (P=0.018) in hcVSMC cultured under calcification conditions (high-phosphate medium) and expressing increased levels of calcification-related genes such as SPP1 (Secreted Phosphoprotein 1, osteopontin) and BMP2 (Bone Morphogenetic Protein 2) when compared with non-calcified hcVSMC. Conclusion Up-regulated levels of miR-6821-5p are found in FH patient with CAC+ atherosclerotic plaques, as well as in calcified isolated human coronary smooth muscle cells that express the pro-calcification genes as osteopontin and BMP2. miR-6821-5p is involved in the development of calcification in the coronary arteries and in the development of atherosclerotic plaques.
Natural history of renal angiomyolipomas in a tertiary center: Our experience during more than 15 years of follow-up
Authors: A. Bravo-Balado, I. Schwartzmann, J. Aumatell, J.D. Subiela, I. Sanz, J. Robalino, E. Moncada, M. Montlleó, J. Salvador, J. Palou, J. Ponce De León Roca
Journal: European Urology (2022)
Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer
Authors: Jeanne Tie, Joshua D. Cohen, Kamel Lahouel, Serigne N. Lo, Yuxuan Wang, Suzanne Kosmider, Rachel Wong, Jeremy Shapiro, Margaret Lee, Sam Harris, Adnan Khattak, Matthew Burge, Marion Harris, James Lynam, Louise Nott, Fiona Day, Theresa Hayes, Sue-Anne McLachlan, Belinda Lee, Janine Ptak, Natalie Silliman, Lisa Dobbyn, Maria Popoli, Ralph Hruban, Anne Marie Lennon, Nicholas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Cristian Tomasetti, Peter Gibbs
Journal: New England Journal of Medicine (2022)

The role of adjuvant chemotherapy in stage II colon cancer continues to be debated. The presence of circulating tumor DNA (ctDNA) after surgery predicts very poor recurrence-free survival, whereas its absence predicts a low risk of recurrence. The benefit of adjuvant chemotherapy for ctDNA-positive patients is not well understood.